Coffee consumption is associated with DNA methylation levels of human blood

Beneficial health effects have been attributed to coffee consumption, but it is not yet known whether epigenetics may have a role in this process. Here we associate epigenome-wide DNA methylation levels to habitual coffee consumption from two studies with blood (2100 and 215 participants), and one with saliva samples (256 participants). Adjusting for age, gender, and blood cell composition, one CpG (cg21566642 near ALPPL2) surpassed genome-wide significance (P=3.7 × 10^-10) and from among 10 additional CpGs significant at P≤5.0 × 10^-6, six were located within 1500 bps of a transcriptional start site. Results for these 11 top-ranked CpGs remained significant after further adjusting for smoking. Also, methylation levels of another 135 CpGs were influenced by both coffee drinking and smoking (P≤1.0 × 10^-7). Functional enrichment analysis suggested that coffee-associated CpGs were located near transcription factor binding (P=1.2 × 10^-6) and protein kinase activity genes (P=2.9 × 10^-5). Interestingly, when we stratified by menopausal hormone therapy (MHT), methylation differences with coffee consumption were observed only in women who never used MHT. We did not replicate any of the associations found in blood in our saliva samples, suggesting that coffee may affect DNA methylation levels in immune cells of the blood but not in saliva.